糖尿病脑缺血再灌注大鼠海马胶质细胞凋亡研究

Study of the Neurogliocyte Apoptosis in Hippocampus under Cerebral Ischemia-reperfusion in Diabetic Rats

目的探讨糖尿病脑缺血再灌注时神经胶质细胞损伤加重的分子机制。方法 96只成年SD大鼠随机分为4组:假手术对照组、正常血糖脑缺血组、糖尿病脑缺血组、PD98059预防糖尿病脑缺血组,每组24只。采用链脲佐菌素诱导糖尿病,双血管闭塞联合放血法建立糖尿病大鼠全脑缺血模型,运用HE染色、TUNEL方法,研究高血糖状态下脑缺血再灌注时和使用P-ERK1/2阻断剂PD98059后海马CA4、CA2神经胶质细胞的凋亡表达状况。结果糖尿病大鼠全脑缺血再灌注时,海马CA4、CA2区神经胶质细胞在缺血15min,再灌注1、3h凋亡细胞数量增加,高于正常血糖脑缺血组大鼠(P<0.05),使用P-ERK1/2阻断剂PD98059后,在缺血再灌注各时间点神经胶质细胞的凋亡细胞表达减少,低于糖尿病脑缺血组(P<0.05)。结论高血糖加重脑缺血再灌注时神经胶质细胞的损伤,高血糖诱导的ERK1/2磷酸化可能介导了神经胶质细胞的凋亡。

Objective To explore the molecular mechanism of the neurogliocytes damage with cerebral ischemia- reperfusion in the diabetic rats. Methods Ninety -six adult SD rats were randomizedly allocated into four groups including sham operation group , normoglycemia operation group , diabetes operation group and PD98059 diabetes operation group（24 rats per group）. Streptozoein was used to induce diabetes, and a whole cerebral isehemia model of diabetic rat was established by the bilateral vascular occlusion combined with bloodletting. H and E staining was used to observe morphological changes, and TUNEL was used to detect the apoptosis of CA2 and CA4 in the hippocampus region of diabetic cerebral ischemia injury by PD98059 and ERK1/2. Results The neuroglial apoptosis of CA2 and CA4 in the hippocampus region among the diabetes groups was significantly higher at 15 minutes after ischemia and 1 h, 3h, 6h after reperfusion compared with the normoglycemia groups（P 〈 0.05 ）. The neurogliocyte apoptosis expression in PD98059 groups was significantly lower than it in the diabetes groups at each time point of cerebral ischemia and reperfusion （P 〈 0.05 ）. Conclusion Hyperglycaemia can increase the neurogliocytes damage of CA2 and CA4 in rat with cerebral is- chemia - reperfusion injury. Phosphorylation of ERK1/2 which was induced by hyperglycaemia possibly led to the neurogliocyte apoptosis of CA2 and CA4 in the hippocampus.